Vibrio vulnificus hemolysin (VvhA) is inactivated in the late growth phase by its oligomerization. Albumin is known to affect the activities of many bacterial toxins. In this study, we investigated the effects of human or bovine serum albumin (HSA or BSA) on the production and activity of VvhA. HSA did not affect V. vulnificus growth and vvhA transcription. However, VvhA hemolytic activity in culture supernatants was significantly higher in the presence of HSA than in the absence of HSA. By Western blot analysis, the oligomerization of VvhA was inhibited and the remaining active VvhA monomer was increased in culture supernatants containing HSA. BSA produced similar results. These findings indicate that both HSA and BSA stabilize VvhA and delay VvhA inactivation by oligomerization, and thus enhance VvhA activity.